Abstract
The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs) propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs). For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs) result in long-term enhancement of spine VGCCs. This activity-dependent VGCC plasticity results in a large interspine variability of VGCC Ca2+ influx. Here, we investigate how spine VGCCs affect glutamatergic synaptic transmission. We combined electrophysiology, two-photon Ca2+ imaging and two-photon glutamate uncaging in acute brain slices from rats. T- and R-type VGCCs were the dominant depolarization-associated Ca2+conductances in dendritic spines of excitatory layer 2 neurons and do not affect synaptic excitatory postsynaptic potentials (EPSPs) measured at the soma. Using two-photon glutamate uncaging, we compared the properties of glutamatergic synapses of single spines that express different levels of VGCCs. While VGCCs contributed to EPSP mediated Ca2+ influx, the amount of EPSP mediated Ca2+ influx is not determined by spine VGCC expression. On a longer timescale, the activation of VGCCs by bAP bursts results in downregulation of spine NMDAR function.
Highlights
The dendritic surface of most excitatory projection neurons is covered with thousands of spines which receive over 90% of glutamatergic synapses (Harris and Kater, 1994)
Depolarization of dendritic spines activates voltage gated Ca2+ channels (VGCCs), both by direct synaptic activation and by electrotonic spread of depolarization mediated by dendritic backpropagating action potentials (bAPs)
We demonstrate that the major VGCC subtypes contributing to bAP Ca2+ transients in layer 2 cells of the medial entorhinal cortex (MEC) are Rand T-type channels
Summary
The dendritic surface of most excitatory projection neurons is covered with thousands of spines which receive over 90% of glutamatergic synapses (Harris and Kater, 1994). Spines and the corresponding synapses are plastic, they undergo activity-dependent functional state changes. This includes spine- and synapse specific structural, morphological and functional changes affecting synapse strength and stability (Alvarez and Sabatini, 2007; Korte and Schmitz, 2016; Segal, 2017). An important signaling molecule related to different types of spine plasticity is VGCC Activation by bAPS Downregulates NMDARs calcium (Ca2+). Spine Ca2+ signals evoked by neuronal activity substantially determine plasticity processes
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have